The overall goal of Project 2 is to establish linkages between fundamental research programs yielding mechanistic insights and a coordinated program of clinical research. We propose to assess the association between inhibitory control functioning (response inhibition) a behavioral function hypothesized to play an important role in addiction, and self-administration of MA by MA-dependent human volunteers in a laboratory setting. We will accomplish this goal by assessing the effects of modafinil, a medication known to enhance inhibitory control functioning, on MA self-administration using a human laboratory model of MA selfadministration. Aim 1. To determine the effects of modafinil treatment on self-administration of MA in a human laboratory model of MA self-administration. Following completion of Project 1 activities (a study of response inhibition and its neurobiological correlates in MA-dependent and control subjects), MA-dependent participants will enter Project 2. The timecourse of the subjective effects of MA following pretreatment with modafinil or placebo will be assessed using self-report rating scales ("high", "crave MA", etc.) because subjective effects of drugs frequently parallel their reinforcing effects. The reinforcing effects of MA (as compared to saline placebo) will be tested using a human laboratory model of drug self-administration originally developed to assess cocaine selfadministration (Walsh et al., 2001), which we have modified to assess MA self-administration Hypothesis: MA will produce greater subjective and reinforcing effects than placebo, and modafinil treatment will reduce these effects of MA. Aim 2. To determine the association between inhibitory control (response inhibition) and MA selfadministration. The effects of modafinil on response inhibition, neural activation via fMRI, and structural MRI will be assessed in Project 1. In Project 2, we will test the association between response inhibition and MA selfadministration behavior during treatment with modafinil or placebo. MA self-administration will be evaluated using a design in which participants must suppress choices for MA in order to receive alternative reinforcers (i.e., money). The outcome of these experiments will experimentally assess the role of deficits in inhibitory control functioning in drug-taking behavior. Hypothesis: Response inhibition will be inversely associated with choices for MA (i.e., poor response inhibition will be associated with increased MA self-administration).